Many delivery systems for the delayed or controlled release of an active substance are currently available. Some state of the art delayed or controlled release systems can be described as membrane controlled systems, which are summarized and described in Robinson & Lee, Controlled Drug Delivery, Mercel Dekker, Inc., New York (1989), pp. 373-421. As the name suggests, these systems comprise a medicament-containing core wherein a membrane or coating encasing the core controls release of the medicament from the system. Typically, these systems give rise to controlled drug release by pores produced in a partially water-soluble polymer. Lieberman, Lachman, & Schwartz, Pharmaceutical Dosage Forms, Mercel Dekker, Inc., New York (1991), pp. 210-213. U.S. Pat. No. 4,756,911 describes a membrane controlled delivery system controlling drug release via an insoluble polymer coating which peels off after contact with gastrointestinal fluid. Medicament release is controlled by diffusion or leaching through a gelatinous mass formed on a water-soluble core.
In contrast, a delivery system commonly known as the matrix system typically contains drug uniformly dispersed in cavities within a polymeric matrix. The matrix system is popular for its effectiveness as well as low cost and ease of manufacture. However, the release behavior of these systems is inherently nonlinear in nature as a result of the decreasing release rate with time due to an increase in diffusional resistance and/or a decrease in effective area at the diffusion front.
Numerous matrix systems have been devised in an effort to achieve linear release of the active substance. Several controlled release systems comprising an active substance dispersed in an insoluble matrix encased by an insoluble coating, in which the active agent is exposed through an aperture in the coating, have been described. For example, a ring shaped system in which the aperature is present in the center of the ring is described in EPA 259219. U.S. Pat. No. 3,851,648 discloses a cylindrical device in which the aperature runs along the length of the cylinder and defines a cavity. A truncated cone in which the small end of the cone is exposed to the dissolving fluid is disclosed in EPB-259113. A pharmaceutical tablet having lenticular form is described in European Pat. No. 0 656 204. The basis for these systems is that the surface area of exposed active agent continuously increases as dissolution proceeds, to compensate for the increased diffusion path between the aperature and the dissolving core.
A device comprising a shaped core containing the active substance encased by an impermeable coating which contains one or more apertures, in which the core geometry is used to control the surface area of the exposed surface is disclosed in EPA-542364.
A three-layered matrix system comprising a shaped core coated with erodible polymeric material is disclosed by Cremer et al., Proceed. Intern. Symp. Control. Rel. Bioact. Mater., 1995, 22, 732-733. In this system, the release profile is controlled by erosion rate of the coating layers and the geometrical shape of the core. The delivery systems described in U.S. Pat. No. 3,317,394 and U.S. Pat. No. 5,114,719 achieve controlled dissolution by erosion of soluble material in the coating to form porous channels.
A coated right cylinder having an exposed circumferential strip is disclosed in U.S. Pat. No. 4,972,448.
A polymeric device for extended delivery of small, water-soluble molecules described in U.S. Pat. No. 5,114,719 controls the drug release by a specific manner of loading the biologically active molecules onto the core.
A matrix system for releasing insoluble drugs into the system in granular form comprising a generally cylindrical core which is coated on one or both faces with an inert or insoluble polymeric material is disclosed in U.S. Pat. No. 4,838,177. The core is obtained by compression of the active substance and a swellable and gellable polymer or mixture of polymers. The release profile in this system is controlled by the high degree of swelling of the core.
European Pat. No. 0 598 309 discloses a matrix system wherein the drug-containing matrix comprises swellable, hydrophilic polymers. Similarly, World Pat. No. 94/06416 describes a pharmaceutical tablet capable of liberating one or more drugs at different release rates consisting of erodible matrix layers containing one or more medicaments. Japanese Publication No. 04360826 describes active substance release by a matrix-type medicine-stored interlayer with release-controlling layers predominant in water-soluble polymers. These tablet systems control release by the high degree of swelling and gelling from polymers in the core.